HIV-1 tropism and CD4 T lymphocyte recovery in a prospective cohort of patients initiating HAART in Ribeirão Preto, Brazil

While human immunodeficiency virus (HIV)-1 chemokine co-receptors 5 tropism and the GWGR motif in the envelope third variable region (V3 loop) have been associated with a slower disease progression, their influence on antiretroviral response remains unclear. The impact of baseline V3 characteristics on treatment response was evaluated in a randomised, double blind, prospective cohort study with patients initiating highly active antiretroviral therapy with lopinavir or efavirenz plus azithothymidine/3TC (1:1) over 48 weeks. Similar virological and immunological responses were observed for both treatment regimens. The 43 individuals had a mean baseline CD4 T cell count of 119 cells/mm(3) [standard deviation (SD) = 99] and a mean viral load of 5.09 log(10) copies/mL (SD = 0.49). The GWGR motif was not associated with a CD4 T cell response, but predicted R5 tropism by the geno2pheno([clinical20%]) algorithm correlated with higher CD4 T cell levels at all monitoring points (p < 0.05). Moreover, higher false-positive rates (FPR) values from this analysis revealed a strong correlation with CD4 T cell recovery (p < 0.0001). Transmitted drug resistance mutations, documented in 3/41 (7.3%) cases, were unrelated to the assigned antiretroviral regimen and had no impact on patient outcomes. In conclusion, na?ve HIV-1 R5 infected patients exhibited higher CD4 T cell counts at baseline; this difference was sustained throughout therapy. The geno2pheno([clinical]) option FPR positively correlated with CD4 T cell gain and may be useful in predicting CD4 T cell recovery.     

A simple method to induce hypoxia-induced vascular endothelial growth factor-A (VEGF-A) expression in T24 human bladder cancer cells

Angiogenesis is an essential process for the establishment, development, and dissemination of several malignant tumors including bladder cancer. The hypoxic condition promotes the stabilization of hypoxia-inducible factor 1 alpha (HIF-1α), which translocates to the nucleus to mediate angiogenic factors including the vascular endothelial growth factor A (VEGF-A). AnaeroGen system was developed for microbiology area to create a low oxygen tension required to the growth of anaerobic bacteria. Here, we hypothesized the use of AnaeroGen system to induce hypoxia in T24 human bladder carcinoma cells, in order to promote the overexpression of VEGF-A. T24 cells were cultured in six-well plates containing McCoy medium. Exposures of T24 cells to hypoxia for 1, 8, 24, and 48 h were performed using the Oxoid AnaeroGen system, while T24 cells under normoxia were used as control. The expression of VEGF-A and HIF-1α was analyzed by real-time PCR. ELISA for HIF-1α was carried out. The VEGF-A expression increased significantly by Oxoid AnaeroGen-induced hypoxia in a time-depending manner, reaching the peak in 48 h of hypoxia. Although HIF-1α mRNA was not changed, HIF-1α protein was increased in the presence of hypoxia, reaching a peak at 8 h. These results demonstrated that the Oxoid AnaeroGen system is a simple method to expose T24 cells to hypoxia and efficiently to upregulate VEGF expression in T24 cells.     

Effect of grazing by isopods and amphipods on growth of Ulva spp. (Chlorophyta)

Eutrophication of shallow coastal waters often leads to blooms of macroalgae. Grazing by crustaceans, such as amphipods and isopods, can reduce macroalgal biomass accumulation. At the same time, growth of the macroalgae can be stimulated by epiphyte removal. The role of grazing by isopods and amphipods on Ulva spp. biomass development was investigated in the Veerse Meer, a brackish lagoon situated in the southwest Netherlands. Exclusion of grazing in the field did not stimulate Ulva spp. growth. In fact, growth rates were higher in exclosures that allowed grazers to enter. Edibility tests identified the amphipod Gammarus locusta, and the isopods Idotea chelipes and Sphaeroma hookeri as potential grazers on Ulva spp. However, when epiphytic diatoms were present on the Ulva spp. thalli, Gammarus and Sphaeroma grazed on ephiphytes and not on Ulva tissue. Only Idotea continued to graze on Ulva spp. A laboratory growth experiment revealed a positive effect of Gammarus presence on Ulva spp. growth, probably caused by preferential removal of epiphytic diatoms from the Ulva spp. thalli. The growth stimulation by epiphyte removing grazers such as Gammarus may explain the higher growth rates in the presence of grazers observed in the field. When determining the potential role of invertebrate grazers in controlling macroalgal biomass accumulation, it is important to include an assessment of the epiphyte abundance on the macroalgae, as preferential removal of epiphytes may stimulate growth and thus have the opposite effect.     

Vitamin D receptor polymorphisms and prostate cancer risk in Brazilian men

Vitamin D seems to be an important determinant of prostate cancer risk and inherited polymorphisms in the 3'untranslated region of the vitamin D receptor (VDR) gene have been associated with the risk and progression of prostate cancer in some populations. We therefore studied VDR gene polymorphisms, as detected by Apal and Taql restriction fragments, in multiethnic Brazilian men (165 patients and 200 controls) for association with prostate cancer risk and parameters of disease severity (serum PSA, Gleason score and tumor stage). No statistical correlations were found. The unique ethnical background of Brazilian subjects, characterized by an extensive racial mixture of European, African-American and Native American, might have blunted any ethnic-specific significance of VDR polymorphisms. Further investigations of the associations between VDR and other genetic or environmental factors are warranted.     

The Fraction of Cancer Attributable to Ways of Life,Infections, Occupation,and Environmental Agents in Brazil in 2020

Many human cancers develop as a result of exposure to risk factors related to the environment and ways of life. The aim of this study was to estimate attributable fractions of 25 types of cancers resulting from exposure to modifiable risk factors in Brazil. The prevalence of exposure to selected risk factors among adults was obtained from population-based surveys conducted from 2000 to 2008. Risk estimates were based on data drawn from meta-analyses or large, high quality studies. Population-attributable fractions (PAF) for a combination of risk factors, as well as the number of preventable deaths and cancer cases, were calculated for 2020. The known preventable risk factors studied will account for 34% of cancer cases among men and 35% among women in 2020, and for 46% and 39% deaths, respectively. The highest attributable fractions were estimated for tobacco smoking, infections, low consumption of fruits and vegetables, excess weight, reproductive factors, and physical inactivity. This is the first study to systematically estimate the fraction of cancer attributable to potentially modifiable risk factors in Brazil. Strategies for primary prevention of tobacco smoking and control of infection and the promotion of a healthy diet and physical activity should be the main priorities in policies for cancer prevention in the country.     

Qualitative analysis of oscillations in isolated populations of flies

Populations oscillations in isolated populations of flies are considered. Qualitative methods of analysis are applied to the functional differential equation representing the system and conditions for the occurrence of oscillations are derived. These conditions are readily visualized in terms of parameters which are easily measured and have a straightforward biological interpretation.     

Social Networks Shape the Transmission Dynamics of Hepatitis C Virus

Hepatitis C virus (HCV) infects 170 million people worldwide, and is a major public health problem in Brazil, where over 1% of the population may be infected and where multiple viral genotypes co-circulate. Chronically infected individuals are both the source of transmission to others and are at risk for HCV-related diseases, such as liver cancer and cirrhosis. Before the adoption of anti-HCV control measures in blood banks, this virus was mainly transmitted via blood transfusion. Today, needle sharing among injecting drug users is the most common form of HCV transmission. Of particular importance is that HCV prevalence is growing in non-risk groups. Since there is no vaccine against HCV, it is important to determine the factors that control viral transmission in order to develop more efficient control measures. However, despite the health costs associated with HCV, the factors that determine the spread of virus at the epidemiological scale are often poorly understood. Here, we sequenced partial NS5b gene sequences sampled from blood samples collected from 591 patients in São Paulo state, Brazil. We show that different viral genotypes entered São Paulo at different times, grew at different rates, and are associated with different age groups and risk behaviors. In particular, subtype 1b is older and grew more slowly than subtypes 1a and 3a, and is associated with multiple age classes. In contrast, subtypes 1a and 3b are associated with younger people infected more recently, possibly with higher rates of sexual transmission. The transmission dynamics of HCV in São Paulo therefore vary by subtype and are determined by a combination of age, risk exposure and underlying social network. We conclude that social factors may play a key role in determining the rate and pattern of HCV spread, and should influence future intervention policies.     

Genotoxicity and mutagenicity of Rosmarinus officinalis (Labiatae) essential oil in mammalian cells in vivo

Rosmarinus officinalis (rosemary) oil is widely used by the cosmetic, food, and pharmaceutical industries as a fragrance component of soaps, creams, lotions, and perfumes. Although it is popular, potential harmful side-effects of the oil have been described. We investigated the genotoxic and mutagenic potential of essential oil of R. officinalis in rodents, using comet, micronucleus and chromosome aberration assays. The animals were treated by gavage with one of three dosages of rosemary oil (300, 1000 or 2000 mg/kg). Liver and peripheral blood cells were collected from Swiss mice 24 h after treatment for the comet assay (genotoxicity endpoint), along with bone marrow cells for the micronucleus test (mutagenicity endpoint). Bone marrow cells were collected from Wistar rats 24 h after oil treatment for the micronucleus and chromosome aberration assays. Based on the comet assay, all three doses of rosemary oil induced significant increases in DNA damage in the mouse cells. There was a significant increase in micronucleated cells and chromosome aberrations only at the two higher doses. We conclude that rosemary essential oil provokes genotoxic and mutagenic effects when administered orally.